This invention provides novel compositions of matter. This invention further provides novel processes for producing these compositions of matter. This invention further provides novel chemical intermediates useful in the above processes.
This invention is specifically concerned with novel bicyclic nitrogen-containing compounds which are analogs of the prostaglandins, e.g., ##STR2## Included within the scope of this invention, in addition to such 9.alpha., 11.alpha.-azo-9,11,15 -trideoxy-PGF-type compounds, are 9.alpha.,11.alpha.-epoxyimino-9,11,15 -trideoxy-PGF-type compounds and N,N'-dialkyl-9.alpha.,11.alpha.-hydrazino-9,11,15-trideoxy-PGF-type compounds, e.g., ##STR3## respectively.
Accordingly, the present invention is concerned with biheterocyclic, nitrogen-containing analogs of the prostaglandins, e.g., 9.alpha., 11.alpha.-azo-, 9.alpha.-11.alpha.-epoxyimino, 11.alpha.-9.alpha.-epoxyimino-, and N,N'-alkyl or alkylcarbonyl-hydrazino-. Thus each of the above compounds is a derivative of prostane which has the following structure and carbon atom numbering ##STR4## For a discussion of the use of the corresponding C-1 carboxylic acid derivatives, i.e., the prostaglandins, see, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. A systematic name for prostanoic acid, the above-mentioned C-1 carboxylic acid, is 7-[2.beta.-octyl)-cyclopen-1.alpha.-yl]-heptanoic acid.
In the above formulas, as well as in the formulas hereinafter given, broken line attachments to the cyclopentane ring indicate substituents in alpha configuration i.e., below the plane of the cyclopentane ring. Heavy solid line attachments to the cyclopentane ring indicate substituents in beta configuration, i.e., above the plane of the cyclopentane ring. The use of wavy lines (.about.) herein will represent attachment of substituents in either the alpha or beta configuration or attachment in a mixture of alpha and beta configurations.
Molecules of the known prostaglandins each have several centers of asymmetry, and can exist in racemic (optically inactive) form and in either of the two enantiomeric (optically active) forms, i.e. the dextrorotatory and levorotatory forms. As drawn, the above formulas each represent the particular optically active form of the prostaglandin as is obtained from mammaliam tissues, for example, sheep vesicular glands, swine lung, or human seminal plasma, from carbonyl and/or double bond reduction of the prostaglandin so obtained. See, for example, Bergstrom et al., cited above. The mirror image of ech of these formulas, represents the other enantiomer of that prostaglandin. The racemic form of a prostaglandin contains equal numbers of both enantiomeric molecules, and one of the above formulas and the mirror image of that formula is needed to represent correctly the corresponding racemic prostaglandin. For convenience hereinafter, use of the term, prostaglandin or "PG" will mean the optically active form of that prostaglandin thereby referred to with the same absolute configuration as PGE.sub.1 obtained from mammalian tissues. When reference to the racemic form of one of those prostaglandins is intended, the work "racemic" or "dl" will precede the prostaglandin name.
The term "prostaglandin-type" (PG-type) product, as used herein, refers to any bicyclic cyclopentane derivative which is useful as an antiinflammatory agent, as indicated herein.
The term prostaglandin-type intermediate, as used herein, refers to any cyclopentane derivative useful in preparing a prostaglandin-type product.
The formulas as drawn herein, which depict a prostaglandin-type product or an intermediate useful in preparing a prostaglandin-type product, each represent the particular stereoisomer of the prostaglandin-type product which is of the same relative stereochemical configuration as a corresponding prostaglandin obtained from mammalian tissues, or the particular stereoisomer of the intermediate which is useful in preparing the above stereoisomer of the prostaglandin-type product.
The term "prostaglandin analog", as used herein, represents that stereoisomer of a prostaglandin-type product which is of the same relative stereochemical configuration as a corresponding prostaglandin obtained from mammalian tissues or a mixture comprising that stereoisomer and the enantiomer thereof. In particular, where a formula is used to depict a prostaglandin-type compound herein, the term prostaglandin analog refers to the compound of that formula, or a mixture comprising that compound and the enantiomer, thereof.
See U.S. Pat. Nos. 3,950,363 and 4,028,350 for a description of 9.alpha.,11.alpha.-or 11.alpha.-9.alpha.-epoxymethano-9,11,15 -trideoxy-PGF compounds corresponding to certain compounds of the present invention. See also E. J. Corey, et al., Biochemistry, 72:3355-3358 (1975) for a disclosure of 9,11-dideoxy-9.alpha.--azo-PGF.sub.2.